Burden of new and recurrent tuberculosis in a major South African city stratified by age and HIV-status.

Aim: To describe the burden of tuberculosis (TB) in Cape Town by calculating TB incidence rates stratified by age and HIV-status, assessing the contribution of retreatment disease and estimating the cumulative lifetime TB risk in HIV-negative individuals.

Methods: Details of TB cases were abstracted from the 2009 electronic TB register. Population denominators were estimated from census data and actuarial estimates of HIV prevalence, allowing calculation of age-specific and HIV-stratified TB notification rates.

Diagnostic accuracy of a low-cost, urine antigen, point-of-care screening assay for HIV-associated pulmonary tuberculosis before antiretroviral therapy: a descriptive study.

Background: The diagnostic accuracy of sputum smear microscopy and routine chest radiology for HIV-associated tuberculosis is poor, and culture-based diagnosis is slow, expensive, and is unavailable in most resource-limited settings. We assessed the diagnostic accuracy of a urine antigen test Determine TB-LAM Ag (Determine TB-LAM; Alere, Waltham, MA, USA) for screening for HIV-associated pulmonary tuberculosis before antiretroviral therapy (ART).

Methods: In this descriptive study, consecutive adults referred to a community-based ART clinic in Gugulethu township, South Africa, were all screened for tuberculosis by obtaining sputum samples for fluorescence microscopy, automated liquid culture (gold-standard test), and Xpert MTB/RIF assays (Cepheid, Sunnyvale, CA, USA) and urine samples for the Clearview TB-ELISA (TB-ELISA; Alere, Waltham, MA, USA) and Determine TB-LAM test.

Antiretroviral treatment as prevention: impact of the 'test and treat' strategy on the tuberculosis epidemic.

Antiretroviral therapy (ART) has been remarkably effective in ameliorating Human Immunodeficiency Virus (HIV)-associated morbidity and mortality. The rapid decline in viral load during ART also presents an opportunity to develop a "treatment as prevention" strategy in order to reduce HIV transmission at a population level. Modelling exercises have demonstrated that for this strategy to be effective, early initiation of ART with high coverage of the HIV-infected population will be required.

High prevalence of self-reported undiagnosed HIV despite high coverage of HIV testing: a cross-sectional population based sero-survey in South Africa.

Objectives: To measure HIV prevalence and uptake of HIV counseling and testing (HCT) in a peri-urban South African community. To assess predictors for previous HIV testing and the association between the yield of previously undiagnosed HIV and time of last negative HIV test

Methods: A random sample of 10% of the adult population (≥15 years) were invited to attend a mobile HCT service. Study procedures included a questionnaire, HIV testing and CD4 counts.

Delays in starting antiretroviral therapy in patients with HIV-associated tuberculosis accessing non-integrated clinical services in a South African township.

Background: Delays in the initiation of antiretroviral therapy (ART) in patients with HIV-associated tuberculosis (TB) are associated with increased mortality risk. We examined the timing of ART among patients receiving care provided by non-integrated TB and ART services in Cape Town, South Africa.

Methods: In an observational cohort study, we determined the overall time delay between starting treatment for TB and starting ART in patients treated in Gugulethu township between 2002 and 2008.

Early outcomes and the virological effect of delayed treatment switching to second-line therapy in an antiretroviral roll-out programme in South Africa.

Background: More patients in resource-limited settings are starting second-line antiretroviral treatment (ART) following first-line ART failure. We aimed to describe predictors of lack of virological suppression in HIV-infected patients on second-line ART in a roll-out programme in South Africa.

Methods: A retrospective analysis was performed on an adult HIV treatment cohort who started second-line ART (lopinavir/ritonavir, didanosine and zidovudine) after virological failure of first-line ART (two consecutive HIV RNA>1,000 copies/ml).

Linkage to HIV care from a mobile testing unit in South Africa by different CD4 count strata.

Background: The linkage and barriers of linkage to facility-based HIV care from a mobile HIV testing unit have not previously been described.

Methods: A stratified random sample (N = 192) was drawn of all eligible, newly diagnosed, HIV-infected individuals with a laboratory CD4 count result on a mobile unit between August 2008 and December 2009. All individuals with CD4 counts ≤350 cells per microliter and 30% of individuals with CD4 counts >350 cells per microliter were sampled.

Accuracy of immunological criteria for identifying virological failure in children on antiretroviral therapy - the IeDEA Southern Africa Collaboration.

Objectives: To determine the diagnostic accuracy of World Health Organization (WHO) 2010 and 2006 as well as United States Department of Health and Human Services (DHHS) 2008 definitions of immunological failure for identifying virological failure (VF) in children on antiretroviral therapy (ART).

Methods: Analysis of data from children (<16 years at ART initiation) at South African ART sites at which CD4 count/per cent and HIV-RNA monitoring are performed 6-monthly. Incomplete virological suppression (IVS) was defined as failure to achieve ≥1 HIV-RNA ≤400 copies/ml between 6 and 15 months on ART and viral rebound (VR) as confirmed HIV-RNA ≥5000 copies/ml in a child on ART for ≥18 months who had achieved suppression during the first year on treatment.

Screening for HIV-associated tuberculosis and rifampicin resistance before antiretroviral therapy using the Xpert MTB/RIF assay: a prospective study.

Background: The World Health Organization has endorsed the Xpert MTB/RIF assay for investigation of patients suspected of having tuberculosis (TB). However, its utility for routine TB screening and detection of rifampicin resistance among HIV-infected patients with advanced immunodeficiency enrolling in antiretroviral therapy (ART) services is unknown.

Methods And Findings: Consecutive adult HIV-infected patients with no current TB diagnosis enrolling in an ART clinic in a South African township were recruited regardless of symptoms.

Provider-initiated HIV testing increases access of patients with HIV-associated tuberculosis to antiretroviral treatment.

Background: Timely initiation of antiretroviral treatment (ART) is a critical component of the case management of patients with HIV-associated tuberculosis (TB) and advanced immunodeficiency. We sought to determine the impact of the introduction of provider-initiated HIV-testing in TB clinics in 2005 on subsequent referrals of patients with HIV-associated TB at a community-based ART service in Cape Town.

Methods: Retrospective analysis of an ART cohort database (2002 - 2008) stratified by calendar periods.

Loss to follow-up in a community clinic in South Africa--roles of gender, pregnancy and CD4 count.

Background: Faith-based organisations have expanded antiretroviral therapy (ART) in community clinics across South Africa. Loss to follow-up (LTFU), however, limits the potential individual and population treatment benefits and optimal care.

Objective: To identify patient characteristics associated with LTFU 6 months after starting ART in a large community clinic.

Virological breakthrough: a risk factor for loss to followup in a large community-based cohort on antiretroviral therapy.

Background. We have previously shown that 75% of individuals on antiretroviral therapy (ART) in a resource-limited setting who experienced virological breakthrough to >1000 copies/mL were resuppressed after an intensive adherence intervention. This study examines the long-term outcomes of this group in order to understand the impact of the adherence intervention over time.

Efavirenz and rifampicin in the South African context: is there a need to dose-increase efavirenz with concurrent rifampicin therapy?

Background: Increasing efavirenz (EFV) dose from 600 mg to 800 mg daily has been suggested with concomitant rifampicin (RFN), as induction of cytochrome P450 isoenzymes may reduce EFV plasma concentrations.

Methods: Individuals from the CIPRA-South Africa cohort taking EFV-based antiretroviral therapy with concomitant tuberculosis (TB) were dosed with either increased (800 mg) or standard (600 mg) dose EFV during TB treatment. After TB therapy, all individuals took 600 mg EFV.

Tuberculosis control has failed in South Africa--time to reappraise strategy.

South Africa's rate of tuberculosis (TB) has increased over the last 20 years, to now having the third-highest TB burden in the world. The TB control programme has primarily focused on effective case management of passively presenting TB cases, and progress has been recorded towards international treatment targets. While outcomes for notified TB cases have improved, this strategy failed to contain the TB epidemic.

Force of tuberculosis infection among adolescents in a high HIV and TB prevalence community: a cross-sectional observation study.

Background: Understanding of the transmission dynamics of tuberculosis (TB) in high TB and HIV prevalent settings is required in order to develop effective intervention strategies for TB control. However, there are little data assessing incidence of TB infection in adolescents in these settings.

Methods: We performed a tuberculin skin test (TST) and HIV survey among secondary school learners in a high HIV and TB prevalence community.

Transmission elasticity in communities hyperendemic for tuberculosis.

Background: Despite consistently meeting international performance targets for tuberculosis case detection and treatment success, areas where tuberculosis is hyperendemic fail to achieve the predicted epidemiological impact. In this article, we explore the anomalous relationship between defined performance targets and actual reduction in tuberculosis transmission.

Methods: In areas where tuberculosis is endemic, poorly ventilated social gathering places such as shebeens (informal alcohol drinking places), minibus taxis, and clinic waiting rooms are all potential transmission hot spots.

Asking the right questions: developing evidence-based strategies for treating HIV in women and children.

In July 2010, the World Health Organization (WHO) issued formal revisions of its guidelines on the use of highly active antiretroviral therapy for HIV. The new guidelines greatly expand eligibility for treatment of adults and children, as well as for pregnant women seeking prophylaxis for vertical HIV transmission. WHO's new recommendations bring the guidelines closer to practices in developed countries, and its shift to earlier treatment alone will increase the number of treatment-eligible people by 50% or more.

Time to initiation of antiretroviral therapy among patients with HIV-associated tuberculosis in Cape Town, South Africa.

We studied the time interval between starting tuberculosis treatment and commencing antiretroviral treatment (ART) in HIV-infected patients (n = 1433; median CD4 count 71 cells per microliter, interquartile range: 32-132) attending 3 South African township ART services between 2002 and 2008. The overall median delay was 2.66 months (interquartile range: 1.

Mother-to-child transmission of HIV in a community-based antiretroviral clinic in South Africa.

Objective: To examine the uptake of ART among pregnant women referred to an ART service and the associated rates and risk factors for vertical HIV transmission.

Method: Retrospective analysis of an observational cohort at a community ART clinic in Cape Town.

Results: Between 2002 and 2008, 367 treatment-naive pregnant women accessed the clinic.

Psychosocial factors influencing breast cancer risk appraisal among older women.

Although the incidence of breast cancer increases with age, many older women are uninformed about the increased risk and have lower mammography screening rates than younger women. Understanding older women's perceptions of risk might assist health care providers in offering appropriate resources that result in screening. In this study, we explored psychosocial components influencing older women's breast cancer risk appraisal.

Optimum time to start antiretroviral therapy in patients with HIV-associated tuberculosis: before or after tuberculosis diagnosis?

WHO policy states that tuberculosis (TB) should be diagnosed and treated before starting antiretroviral treatment (ART). However, during the pre-ART screening period, diagnosing or excluding TB can be a lengthy process and may cause undesirable delays in ART initiation. In this observational study from South Africa, we report that initiation of ART before TB treatment in patients with delayed diagnoses of culture-positive prevalent TB was not associated with adverse clinical, immunological or virological outcomes during 12-month follow-up.

Antiretroviral therapy and TB notification rates in a high HIV prevalence South African community.

Background: Antiretroviral therapy (ART) has been proposed as an intervention for reducing tuberculosis (TB) burdens in areas with high HIV prevalence. However, little data is available on the impact of ART on population-level TB.

Methods: Trends in adult TB case fatality and notifications were assessed before and during increasing ART coverage in a well-defined periurban community, from 1997 to 2008.